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梭曼、沙林和塔崩对大鼠纹状体中环核苷酸代谢的急性影响。

Acute effects of Soman, Sarin, and Tabun on cyclic nucleotide metabolism in rat striatum.

作者信息

Liu D D, Watanabe H K, Ho I K, Hoskins B

出版信息

J Toxicol Environ Health. 1986;19(1):23-32. doi: 10.1080/15287398609530903.

DOI:10.1080/15287398609530903
PMID:2875191
Abstract

Rats were injected sc with 120 micrograms/kg Soman, 120 micrograms/kg Sarin or 240 micrograms/kg Tabun. At 15 min, 2 h, or 6 h after administration, animals were decapitated along with saline-treated controls, and striatal activities of nucleotide cyclases and phosphodiesterases and striatal cyclic nucleotide levels were determined. All three agents had two similar effects on rat striatal cyclic nucleotide systems: they all increased cyclic GMP levels 15 min after their administration, and they all decreased guanylate cyclase activity 2 h after administration. There were also some different effects elicited by these three organophosphorus compounds. Different effects of Soman and Sarin seem to be mainly due to their different potencies, which in turn influence the time course of their actions. Tabun is quite different from Soman and Sarin in several respects: it rarely causes convulsions at sub-lethal doses, it has no effects on striatal cyclic AMP levels, and it affects enzyme activities 6 h after its administration. These differences may be due to the presence of cyanide instead of fluoride in its structure: i.e., this may be responsible for the different effects of Tabun on striatal cyclic nucleotide systems, and perhaps other biochemical effects. These results also indicate that other neurotransmitter systems, in addition to the cholinergic system, may be involved in organophosphate-induced toxicity.

摘要

给大鼠皮下注射120微克/千克的梭曼、120微克/千克的沙林或240微克/千克的塔崩。给药后15分钟、2小时或6小时,将动物连同生理盐水处理的对照动物一起断头,并测定纹状体中核苷酸环化酶和磷酸二酯酶的活性以及纹状体中环核苷酸的水平。所有这三种药剂对大鼠纹状体环核苷酸系统都有两个相似的作用:给药后15分钟它们都使环鸟苷酸水平升高,给药后2小时它们都使鸟苷酸环化酶活性降低。这三种有机磷化合物也产生了一些不同的作用。梭曼和沙林的不同作用似乎主要是由于它们的效力不同,这反过来又影响了它们作用的时间进程。塔崩在几个方面与梭曼和沙林有很大不同:它在亚致死剂量下很少引起惊厥,对纹状体环磷酸腺苷水平没有影响,并且在给药后6小时影响酶活性。这些差异可能是由于其结构中存在氰化物而非氟化物:即,这可能是塔崩对纹状体环核苷酸系统产生不同作用以及可能产生其他生化作用的原因。这些结果还表明,除胆碱能系统外,其他神经递质系统可能也参与了有机磷诱导的毒性作用。

相似文献

1
Acute effects of Soman, Sarin, and Tabun on cyclic nucleotide metabolism in rat striatum.梭曼、沙林和塔崩对大鼠纹状体中环核苷酸代谢的急性影响。
J Toxicol Environ Health. 1986;19(1):23-32. doi: 10.1080/15287398609530903.
2
Comparison of the effects of diisopropylfluorophosphate, sarin, soman, and tabun on toxicity and brain acetylcholinesterase activity in mice.二异丙基氟磷酸酯、沙林、梭曼和塔崩对小鼠毒性及脑乙酰胆碱酯酶活性影响的比较。
J Toxicol Environ Health. 1989;26(4):437-46. doi: 10.1080/15287398909531267.
3
Acute effects of soman, sarin, and tabun on microsomal and cytosolic components of the calmodulin system in rat striatum.
J Neurochem. 1986 Jan;46(1):265-9. doi: 10.1111/j.1471-4159.1986.tb12956.x.
4
An assessment of comparative acute toxicity of diisopropyl-fluorophosphate, tabun, sarin, and soman in relation to cholinergic and GABAergic enzyme activities in rats.二异丙基氟磷酸酯、塔崩、沙林和梭曼对大鼠胆碱能和γ-氨基丁酸能酶活性的比较急性毒性评估。
Fundam Appl Toxicol. 1984 Aug;4(4):531-8. doi: 10.1016/0272-0590(84)90042-3.
5
Variability of neurotoxicity of and lack of tolerance to the anticholinesterases soman and sarin in the rat.大鼠体内抗胆碱酯酶索曼和沙林的神经毒性变异性及耐受性缺失
Res Commun Chem Pathol Pharmacol. 1985 Jun;48(3):415-30.
6
Relationship between the neurotoxicities of Soman, Sarin and Tabun, and acetylcholinesterase inhibition.梭曼、沙林和塔崩的神经毒性与乙酰胆碱酯酶抑制作用之间的关系。
Toxicol Lett. 1986 Feb;30(2):121-9. doi: 10.1016/0378-4274(86)90094-9.
7
Evidence that changes in levels of cyclic nucleotides in the CNS are not related to soman-induced convulsions.中枢神经系统中环状核苷酸水平的变化与梭曼诱发惊厥无关的证据。
Neurotoxicology. 1988 Spring;9(1):23-37.
8
Neurobehavioral toxicity with low doses of sarin and soman.
Methods Find Exp Clin Pharmacol. 1990 May;12(4):245-50.
9
Studies on low dose sub-acute administration of soman, sarin and tabun in the rat.
Acta Pharmacol Toxicol (Copenh). 1985 Oct;57(4):234-41. doi: 10.1111/j.1600-0773.1985.tb00037.x.
10
Hypersensitivity to antimuscarinic agents following brief exposure to Soman and Sarin.
J Toxicol Environ Health. 1986;18(1):103-9. doi: 10.1080/15287398609530851.